(S)-Pregabalin, 3-(aminomethyl)-5-methyl-(3S)-hexanoic acid, which is also known as (S)-(+)-3-(aminomethyl)-5-methylhexanoic acid, has the empirical formula C8H17NO2 and a molecular weight of 159, and may be represented by the chemical structure:

(S)-Pregabalin has been developed as a follow-up compound to Gabapentin, NEURONTIN®, for use in the treatment of epilepsy, pain, anxiety, and social phobia. Both (S)-Pregabalin and gabapentin are analogs of 4-aminobutyric acid (GABA), a neurotransmitter that is thought to play a major inhibitory role in the central nervous system (CNS). (S)-Pregabalin (PRG) has been approved in US for the treatment of nerve pain associated with diabetes and shingles, as of Dec. 31, 2004. (S)-Pregabalin is available as LYRICA™ in tablets for 25, 50, 75, 150, 200, and 300 mg doses.
(S)-Pregabalin, which is also known as γ-amino butyric acid or (S)-3-isobutyl GABA, has been found to activate GAD (L-glutamic acid decarboxylase), has a dose dependent protective effect on-seizure, and is a CNS-active compound. (S)-Pregabalin has been found to be useful in anticonvulsant therapy, due to its activation of GAD, promoting the production of GABA, one of the brain's major inhibitory neurotransmitters, which is released at 30 percent of the brains synapses. (S)-Pregabalin has analgesic, anticonvulsant, and anxiolytic activity.
The preparation of (S)-Pregabalin described in DRUGS OF THE FUTURE, 24 (8), 862-870 (1999) is done according to the following scheme:
wherein, (R)-(−)-3-(carbamoylmethyl)-5-methylhexanoic acid of formula 5, a key intermediate in the synthesis, is converted to (S)-Pregabalin via a Hoffmann degradation with Br2/NaOH, followed by precipitation of (S)-Pregabalin, after addition of HCl.
A very similar process is disclosed in U.S. Pat. No. 5,616,793, wherein (S)-Pregabalin is also obtained by the Hoffman degradation, followed by precipitation of (S)-Pregabalin, after addition of HCl. The product is further purified by crystallization from a mixture of isopropanol and water.
Hence, there is a need in the art for a process for the preparation and purification of Pregabalin and salts thereof.